Drugs to Treat Inflammation Flashcards
What do glucocorticoids inhibit?
Arachidonic acid release and metabolism
What do NSAIDs inhibit?
Cyclo-oxygenases
What do cysteinyl leukotriene 1 receptor antagonists inhibit?
LTD4 and LTD5 actions
Why are prostaglandins not commonly used as a drug?
Too unstable and expensive
What prostaglandin is used in pulmonary hypertension?
Epoprostenol PGI2 analogue
What are the effects of NSAIDs?
Anti-inflammatory = palliative for manifestations of inflammation
Analgesic - limit hyperalgesic effects of prostaglandins
Anti-pyretic
What are the indications for NSAIDs as an anti-inflammatory?
Acute and chronic conditions
- Rheumatoid arthritis
- Gout > NOT aspirin
Why is aspirin not used in gout?
Competes with uric acid for transporter > makes condition worse
When are NSAIDs indicated as an analgesic?
Headache
Menstrual pain
Musculoskeletal pain
Are NSAIDs curative?
No, palliative
What are the gastro-protective roles of PGE2?
Increases mucus secretion
Reduces gastric acid secretion
Promotes blood flow
Promotes angiogenesis
How do NSAIDs cause cause gastrointestinal adverse effects?
Inhibit mucosal synthesis of PGI2 and PGE2
How do NSAIDs increase bleeding time?
Decrease TXA2 synthesis > impaired platelet aggregation
How do NSAIDs cause renal and vascular adverse effects?
Compromise renal blood flow
- Decrease prostacyclin dilation
Increase blood pressure
- Decrease PGE2 natriuresis
When may NSAIDs cause renal failure?
Hypovolaemic
Underlying renal disease
Heart failure
In which demographic is renal failure caused by NSAIDs more common?
Elderly
What is aspirin-sensitive asthma?
Respond to NSAIDs with bronchospasm
What proportion of people with asthma are affected with aspirin-sensitive asthma?
10%
How does asprin resolve inflammation?
Suppression of pro-inflammatory compounds
Promotion of substances that resolve inflammation
Why is aspirin use contra-indicated in children?
Reye’s syndrome
- Liver toxicity, particularly associated with viral infection in children under 12
How are aspirin-triggered lipoxins formed?
Acetylated COX2
What are aspirin-triggered lipoxins?
Inflammation-resolving lipids
Aren’t usually made
How does the use of aspirin in cardiovascular disease work?
Increases ratio of PGI2/TXA2 in blood vessels, via loss of COX activity in platelets, which - Selectively reduces thromboxane - Prostacyclin preserved Dilates vessels Diminishes platelet reactivity
What are the effects of paracetamol?
Analgesic
Anti-pyretic
Which demographic is paracetamol especially used in?
Children
Does paracetamol have anti-inflammatory effects?
No
What is the mechanism of action of paracetamol?
Still uncertain
What does paracetamol cause in overdose?
Irreversible liver failure
What are the differences between different structural classes of NSAIDs?
Potency
Half lives
Make them more or less helpful in different applications
What are the indications for glucocorticoids?
Physiological replacement; eg: Addison's disease Anti-inflammatory - Asthma - Topical - Hypersensitivity states - Rheumatoid arthritis
What is the mechanism of action of glucocorticoids?
Gene regulatory effects > anti-inflammatory effects
- Transactivation
- Transrepression
What is transactivation in terms of glucocorticoid action?
Transcription factors interact with promoter regions of target genes
What is transrepression in terms of glucocorticoid action?
Protein-protein interaction
Glucocorticoid receptor binds to pro-inflammatory transcription factors > blocks their effects
What is neutralisation of TNF-alpha used as a treatment in?
Rheumatoid arthritis
What are the adverse effects of neutralisation of TNF-alpha?
Reactivation of latent TB
Other developing infections need aggressive antibiotic treatment
